Abstract
Process parametric release is widely accepted as an alternative to end-product biologic sterility testing of injectable products. Based upon 12D overkill conditions (which according to USP XXI is 15 min at 121 °C in an autoclave employing saturated steam under pressure) and a Z value = 10 °C for thermally resistant micro-organisms, the enthalpy of deactivation (E) using Arrhenius treatment of first-order decay kinetics was determined to be about 71 kilocalories/mole in the temperature range for steam sterilization. The following equation was derived for determining the biologic F0 value at any temperature (T) based upon an initial bioburden (N0) and the probability of finding a surviving organism (Ns) and having an exhibited D value at the standard sterilizing temperature of 121 °C:log(N0/Ns) = F0/D121 • exp-E/1-87(1/T -I/394.2). For example at T = 116°C and D121°C = 1.25 min, the resulting F0 value for 12D overkill conditions was calculated to be 47 min at 116 ° C. The heat-up time from 25 °C to 121 °C was also calculated for an injectable solution in a glass vial placed in a conventional, isothermal, steam-jacketed, autoclave using the combined heat-transfer equation for energy and mass transfer. The overall heat-transfer coefficient (U)for type I, borosilicate glass vials was determined to be 0.0026 cal/cm/cm2 · s · °C. In addition, the heat-up time for 50% dextrose in water was also calculated by first estimating the specific heat (Cp) of the solution according to the method of Chueh and Swanson (Can. J. Chem. Eng. 1973). Using a similar process parametric approach, a preliminary estimate appears to indicate that B. subtilis spores having a Z value = 20 °C may not be an appropriate biologic indicator for dry heat sterilization, because its enthalpy of deactivation is only about 36 kilocalories/mole at this Z value.
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